Atherosclerosis, the principal contributor to the pathogenesis of myocardial and cerebral infarction, is known to be one of the leading causes of morbidity and mortality worldwide. Elevated plasma concentration of cholesterol, especially low density lipoprotein (LDL) and triglyceride is recognized as a leading cause in the development of atherosclerosis and coronary heart disease. (Cholesterol and Mortality: 30 years of Follow-up from the Framingham Study, Anderson, Castelli, & Levy, JAMA, Vol. 257, pp. 2176-80 (1987). These conditions are responsible for one-third of deaths in industrialized nations. (Eghdamian, E.; Ghose, K. Drugs Today, 1998, 34, pp. 943.)
Several drugs are being used in the treatment of dyslipidemia. The drugs can intervene by lowering cholesterol (LDL and total cholesterol) or by lowering triglyceride levels in plasma. Treatment of hyperlipidemia using statins has been used to lower serum levels of cholesterol and triglyceride. Statins such as atorvastatin, lovastatin, fluvastatin, simvastatin and pravastatin are HMG CoA reductase inhibitors which act by inhibiting cholesterol synthesis and upregulate LDL receptors in livers. However, common side effects of statins are myositis, arthralgias, gastrointestinal upset and elevated liver function tests. The fibric acid derivatives, e.g., Clofibrate, gemfibrozil, fenofibrate and ciprofibrate, stimulate lipoprotein lipase that breaks down lipids in lipoproteins and may decrease very low density lipoproteins (VLDL) synthesis. Fibric acid derivatives are used to treat elevated triglyceride levels and among the side effects are myositis, gastrointestinal upset, gallstones and elevated liver function tests. Other drug types used for treatment of hyperlipidemia are bile acid binding resins e.g. cholestyramine and cholestipol. Bile acid binding resins promote bile acid secretion and they increase LDL receptors in the liver. Common side effects are bloating, constipation and elevated triglycerides. Also, Nicotinic acid decreases VLDL synthesis and is used for treatment of elevated LDL and VLDL. Among the prominent side effects of nicotinic acid are cutaneous flushing, gastrointestinal upset, abnormality in liver, elevated glucose and uric acid. Thus, there is a need for the therapeutic benefits of several anti-dyslipidemic drugs while simultaneously reducing the severe side effects.
All publications referred to herein are incorporated herein to the extent not inconsistent herewith for purposes of enablement and written description.